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Characteristics of cefazolin inoculum effect-positive methicillin-susceptible staphylococcus aureus infection in a
1Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
Abstract:
Cefazolin treatment failure has been observed in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) with a cefazolin inoculum effect (CIE). However, data on the characteristics and risk factors for the acquisition of CIE-positive MSSA infection are scarce. CIE positivity was measured as an MIC ≥ 16 μg/ml with a high inoculum (∼5 × 107 CFU/ml). The blaZ gene type was assessed through sequence analysis. The clinical characteristics and risk factors for the acquisition of CIE-positive MSSA infection were assessed. The association between the antimicrobial susceptibility profile and CIE positivity was evaluated. A total of 303 MSSA bacteraemia cases and their corresponding isolates were collected from ten hospitals: 61 (20.1 %) isolates showed a positive CIE; 254 (83.8 %) were positive for the blaZ gene. No significant association was found between CIE positivity and the site of infection. Metastatic cancer (aOR 2.86, 95 % CI, 1.10-7.48) and recent (≤1 month) close contact with a chronically ill patient (aOR 4.69, 95 % CI, 1.76-12.50) were identified as significant risk factors for CIE-positive MSSA infection through multivariate analyses. Resistances to clindamycin (OR 3.55, 95 % CI, 1.62-7.80) and erythromycin (OR 5.00, 95 % CI, 2.50-9.99) were associated with CIE positivity, presenting high specificity (92.9 %) and a negative predictive value (82.3 %). CIE-positive MSSA constituted approximately one-fifth of MSSA bacteraemia cases. Although CIE positivity was not clinically discernible, CIE positivity was associated with clindamycin or erythromycin susceptibility. Therefore, our findings suggest that cefazolin can be used in the treatment of high-inoculum MSSA infection if the isolates are susceptible to clindamycin or erythromycin.
Insights
Cefazolin treatment failure in Staphylococcus aureus infections can occur due to cefazolin inoculum effect (CIE). However, cefazolin may still be effective for high-inoculum infections if the bacteria are susceptible to clindamycin or erythromycin.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Cefazolin treatment failure is noted in high-inoculum infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) exhibiting a cefazolin inoculum effect (CIE).
- Limited data exists on the characteristics and risk factors associated with CIE-positive MSSA infections.
Purpose of the Study:
- To investigate the clinical characteristics and risk factors for acquiring CIE-positive MSSA infections.
- To evaluate the association between antimicrobial susceptibility profiles and CIE positivity.
Main Methods:
- Analysis of 303 MSSA bacteremia cases from ten hospitals.
- CIE positivity determined by MIC ≥ 16 μg/ml at a high inoculum (∼5 × 10^7 CFU/ml).
- Assessment of blaZ gene type, clinical characteristics, risk factors, and antimicrobial susceptibility.
Main Results:
- 61 (20.1%) of MSSA isolates showed positive CIE.
- Metastatic cancer and recent close contact with chronically ill patients were significant risk factors for CIE-positive MSSA infection.
- Resistance to clindamycin and erythromycin was associated with CIE positivity, showing high specificity and negative predictive value.
Conclusions:
- CIE-positive MSSA infections represent approximately one-fifth of MSSA bacteremia cases.
- While CIE positivity is not clinically obvious, it correlates with clindamycin or erythromycin susceptibility.
- Cefazolin can be considered for high-inoculum MSSA infections when isolates are susceptible to clindamycin or erythromycin.
